Differential induction of interleukin-12, interleukin-18, and interleukin-1 beta converting enzyme mRNA in experimental autoimmune encephalomyelitis of the Lewis rat

Experimental autoimmune encephalomyelitis (EAE) is a model of autoimmune ce ntral nervous system (CNS) disease that is mediated by autoreactive Th1 cel ls secreting the proinflammatory cytokine interferon (IFN)-gamma. Interleuk in (IL)-12 in its heterodimeric p35/p40 isoform and the recently described cytokine IL-18 potently induce T cell production of IFN-gamma. Interleukin- 1 beta converting enzyme (ICE) is required to convert IL-18 precursor prote in into its biologically active mature form. In this study, we used semiqua ntitative reverse transcriptase-polymerase chain reaction to determine stea dy state levels of IL-12, IL-18, and ICE mRNA in the spinal cord of Lewis r ats at different stages of EAE. In control rats, we found significant IL-18 , ICE, and IL-12p35, but not IL-12p40 mRNA expression. IL-18 mRNA increased during the acute stage of EAE together with a marked induction of ICE mRNA . IL-12p35 mRNA levels did not change significantly throughout the course o f EAE. Surprisingly, the peak expression of IL-12p40 mRNA was delayed by se veral days relative to the peak of T cell infiltration and IFN-gamma mRNA s ynthesis. Our data implicate the IL-18/ICE pathway in the amplification of Th1-mediated immune responses in the CNS but suggest a differed, so far und efined role of endogenous IL-12 in the late effector phase of EAE. (C) 1998 Elsevier Science B.V. All rights reserved.